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We engineered integrase-deficient lentiviruses to act as vectors for the delivery of large gene knock-ins via homology-directed repair. This technology enables the non-cytotoxic, targeted insertion of difficult-to-express transgenes into genomic loci that are essential to cell survival, thereby overcoming the gene silencing that otherwise limits primary immune cell engineering.
We developed exponentially amplified rolling circle amplification with CRISPR–Cas12a as a one-pot, isothermal assay for microRNA detection. This method has single-digit femtomolar sensitivity and single-nucleotide specificity, and can be deployed for point-of-care testing. The assay has been adapted for the microRNA profiling of extracellular vesicles, which is used in the diagnosis of pancreatic cancer.
INSPECTR is a technique for detecting nucleic acids that couples the sensitivity and specificity of nucleic acid splinted ligation with the versatile readouts of cell-free gene expression. The result is an ambient-temperature workflow that enables the detection of pathogenic viruses at low copy numbers.
An assay leveraging the target-specific splinted ligation of DNA probes to generate expression cassettes for the cell-free synthesis of reporter proteins accurately detects nucleic acids at ambient temperature.
A high-throughput method leveraging peptide-encoding mRNA barcodes for the in vivo screening of libraries of nanoparticle formulations allows for the rapid optimization of a lipid nanoparticle for the delivery of mRNA to the liver.
Ensembles of explainable machine-learning models increase the quality of explanations for the molecular basis of synergetic drug combinations, as shown for the treatment of acute myeloid leukaemia.
An anti-inflammatory enzyme fused with a tissue-anchoring protein and injected into inflamed tissues ameliorates local inflammation without causing systemic immune suppression, as shown in multiple rodent models of inflammatory diseases.
A method leveraging an integrase-deficient lentivirus, homology-directed repair and the electroporation of a CRISPR-associated ribonucleoprotein complex allows for the knock-in and stable expression of large payloads in primary human cells.
The sensitivity, chemical specificity and spatiotemporal resolution of proton magnetic resonance spectroscopic imaging at 7 T allow for the discrimination of deuterated and non-deuterated neurotransmitters and glucose metabolites in the human brain.
A rapid one-pot isothermal assay that leverages rolling-circle amplification and the endonuclease Cas12a can accurately detect specific miRNAs in extracellular vesicles in patient plasma.
A tether-less and battery-less implant allows for the recording of electroencephalograms, electromyograms and body temperature in freely moving small animals, and for closed-loop neuromodulation via optogenetics and pharmacology.
The throughput of the in vivo screening of hydrogels for antifibrotic properties can be increased by tagging the biomaterials with cells and reading their genotype via next-generation sequencing.
The yields of edited primary human lymphocytes can be increased substantially, with respect to those obtained via electroporation, by delivering a CRISPR ribonucleoprotein alongside an amphiphilic peptide identified via screening.
Durable anti-tumour responses can be triggered by maximizing the cooperative phagocytic potency of macrophages through the disruption of the CD47–SIRPα macrophage checkpoint and by delivering a tumour-opsonizing monoclonal antibody.
This Review discusses the characteristics of neural probes that are most likely to facilitate the clinical translation of invasive neural interfaces, the abiotic and biotic factors that contribute to their failure and emerging neural-interface architectures.
Prime editing can efficiently correct the sickle-cell allele to produce wild-type haemoglobin in patient haematopoietic stem cells that engraft efficiently in mice, yielding erythrocytes resistant to hypoxia-induced sickling.